Complexes between gadolinium or other paramagnetic metal ions and organic chelating ligands are widely used as magnetic resonance (MR) contrast agents. Typically, a gadolinium contrast agent increases MR contrast by increasing the nuclear magnetic relaxation rates of water protons that are accessible to the contrast agent during MRI (Caravan, P., et al., R. B. Chem. Rev. 99, 2293 (1999)). The relaxation rate of these protons increases relative to water protons that are not accessible to the contrast agent. This change in relaxation rate leads to improved contrast of the images. In addition, this increase in relaxivity within a specific population of water molecule protons can result in an ability to collect more image data in a given amount of time, resulting in an improved signal to noise ratio.
Because MR contrast agents are treated as drugs by regulatory agencies (e.g., FDA), they undergo extensive clinical testing to assure efficacy and safety. In this regard, certain drugs, e.g., thalidomide, have been shown to have differing safety and/or efficacy profiles depending on whether the drug is an enantiomeric mixture of isomers, or is an optically pure or optically enriched isomer composition (e.g., preferentially the R or S isomer at a particular stereocenter). Thus, it would be useful to have methods to prepare and purify optically enriched or optically pure MRI contrast agent compositions, including those capable of demonstrating increased relaxivity in vitro and in vivo.